Cardioprotective effect of adenosine in ischemia and reperfusion injury

腺苷对缺血再灌注损伤的心脏保护作用

• 批准号: 05454272
• 负责人: INOUE Michitoshi
• 金额: $ 4.35万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454272/
• 关键词: adenosine.; ischemic preconditioning.; alpha1-adrenoceptor.; 5'-nucleotidase; 虚血・再潅流障害; 5'-nucleotidase

We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. We tested whether alpha1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size -limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning that in the control group, even though no difference existed in endomyocardial collateral flow during ischemic. Ectosolic 5'-nucleotidase activity was increased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning. Intermittent alpha1-adrenoceptor stimulation by methoxamine mimicked the increase in 5'-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta, -methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model. Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha1-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning.

我们已经报道缺血预处理可能通过增加5 '-核苷酸酶活性来限制梗死范围。我们测试了在缺血预处理中α 1肾上腺素受体的刺激是否通过增加5 '-核苷酸酶活性介导了梗死面积限制效应。82只犬行冠状动脉结扎4次，每次5 min，间隔5 min再灌注（缺血预处理）。然后闭塞冠状动脉90 min，再灌注6 h。缺血预处理后，尽管缺血期间内膜侧支血流无差异，但按危险区标准化的血管体积小于对照组。缺血预处理后胞质5 '-核苷酸酶活性增加。然而，哌唑嗪减弱了缺血预处理的梗死范围限制作用。甲氧胺间歇性刺激α 1-肾上腺素能受体可模拟5 '-核苷酸酶活性的增加和梗死面积限制作用，而α，β，-亚甲基腺苷5'-二磷酸可消除这种作用。在有意识的模型中得到了相同的结果。因此，我们得出结论，由于α 1-肾上腺素能受体激活导致的胞外5 '-核苷酸酶活性增加可能有助于缺血预处理的梗死面积限制作用。

项目成果

M.Kitakaze: "Superoxide dismutase enhances both adenosine release and coronary hypermic flow through protection of 5'-nucleotidase against its degradation during reperfusion followin ischemia in dogs" Biorheology. 30. 359-370 (1994)

M.Kitakaze：“超氧化物歧化酶通过保护 5-核苷酸酶在狗缺血后的再灌注过程中防止其降解，增强腺苷释放和冠状动脉高血流”生物流变学。

Masafumi Kitakaze: "Infarct size‐limiting effect of ischemic preconditioning is blunted by inhibition of 5′‐nucleotidase activity and attenuation of adenosine release" Circulation. 89. 1237-1246 (1994)

Masafumi Kitakaze：“通过抑制 5-核苷酸酶活性和减弱腺苷释放，可以减弱缺血预处理对梗死面积的限制作用”循环。 89. 1237-1246 (1994)

Masatsugu Hori: "Long-term clinical effect of nilvadipine in patients with chronic heart failure : a double-blind placebo-controlled study" Heart & Vessels. 9. 249-253 (1994)

Masatsugu Hori：“尼伐地平对慢性心力衰竭患者的长期临床效果：双盲安慰剂对照研究” Heart

Masafumi Kitakaze: "Role of adenosine and its interaction with α-adrenoceptor activity in ischemic and reperfusion injury of the myocardium" Cardiovascular Research. 27. 18-27 (1993)

Masafumi Kitakaze：“腺苷的作用及其与 α-肾上腺素受体活性在心肌缺血和再灌注损伤中的相互作用”《心血管研究》27. 18-27 (1993)。

Masafumi Kitakaze: "Ischemic preconditioning increase adenosine release and 5'-nucleotidase activity during myocardial ischemia and reperfusion." Circulation. 87. 208-215 (1993)

Masafumi Kitakaze：“缺血预处理会增加心肌缺血和再灌注期间的腺苷释放和 5-核苷酸酶活性。”